This Web Page is for summaries of the 2 monthly Concord Dependency Seminars held in Western Sydney between 1999 and 2010. From January 2011 these seminars have transferred to Royal Prince Alfred Hospital and are convened by Dr Richard Hallinan and Prof Paul Haber.

This seminar was titled The Other Hepatitis, reflecting the lower prevalence of Hepatitis B compared with Hepatitis C among people using addiction treatment services, and the lower profile of HBV in the community.

In contrast to the vigorous response in recent years to hepatitis C (HCV) in Australia, the response to hepatitis B (HBV) has lagged behind, despite important recent developments in understanding of HBV, in diagnostic tests and antiviral treatments, and desite its large disease burden, especially chronic liver disease and liver cancer.

There are many contrasts between HBV and HCV. Whereas HCV in Australia consists of two 'epidemics' - an older group of people born overseas in endemic areas and a younger group of injecting drug users - about half the prevalence of HBV is among Australians born overseas in endemic areas, especially China and SE Asia but also the Middle east and Mediterranean. Only 5% of chronic HBV is among IDUs; another 8% among men who have sex with men (MSM) and a staggering 16% among indigenous Australians.

The picture is different for new infections (incidence) of HBV in Australia: 44% of these happen among IDU (showing the importance of catch-up vaccination for non-immune people in this risk group) and 35% are through sexual transmission, disproportionately among MSM, but the majority still through heterosexual sex.

The total number of people in Australia with chronic HCV is fairly reliably estimated to be between 200,000 and 250,000, while estimates for HBV range more widely between 90,000 and 160,000, reflecting in part poor knowledge of HBV and low levels of testing among some of the high risk groups.

HBV is a DNA virus, where HCV is an RNA virus. HCV is essentially blood-to-blood transmission, particularly by unsafe injecting, and rarely by sexual transmission, while HBV is spread by contact with infected body fluids including blood, semen and saliva. HBV is thus sexually transmitted, but also by vertical transmission (mother to child), horizontally (close personal contact especially in childhood eg cuts, sores) and by IDU.

Of people infected with HCV, 20-30% spontaneously clear the virus, usually within 6 months, and regardless of their age at infection, without however developing immunity (ie they can be reinfected with HCV). Few people develop clinically evident acute hepatitis. By contrast, for HBV progression to chronic infection is strongly related to age at infection: 80-90% of children infected perinatally develop chronic HBV, with lower rates (30%) of chronicity after infection under the age of 5 years; only 6% of older children and adults develop chronic HBV. Most adults who are infected with HBV develop clinically evident acute hepatitis.

Unlike HCV where late clearance of the virus is unknown, a small percentage of people with chronic HBV clear the virus and develop immunity each year.

HBV and HVC are similar in that a subset of people develop chronic liver inflammation which may slowly progress to cirrhosis and liver failure in a minority of cases, and which increases the risk of development of hepatocellular carcinoma (HCC).

The diagnostic tests for HBV, and the natural history of the disease, while rather more complicated than for HCV, have become clearer in recent years. Chronic HBV is now though of as having 4 phases, with gradual progression through the first 2 phases "immune tolerant" and "immunoactive" into the third phase called "immune control" and sometimes progression into a fourth phase called "immune escape".

In the "immune tolerant" phase, there are high levels of HBV-DNA in the blood but little inflammation of the liver (so liver enzymes like ALT are low or normal). The body is not really fighting the virus. This phase is prolonged in people who get HBV perinatally (20 years or more) but is usually much shorter in adult infections.

In the "immunoactive" phase, DNA levels and liver inflammation (ALT) tend to fluctuate. The body is fighting the virus and the liver is in the wars. This can go on for many years, and this is when much of the liver damage from HBV develops.

If the body develops "immune control", viral DNA drops to undetectable levels and the liver function tests normalise. This phase can go on for decades and is associated with no progression of liver disease.

Unfortunately in some people HBV escapes from immune control. In the "immune escape" phase, viral DNA is detectable again and the ALT indicates liver inflammation. People in this phase of HBV often have the most seriously progressive disease.

In making a diagnosis of HBV and working out which phase a person is in, 3 types of tests are used: serological tests, liver function tests (especially ALT for inflammation), and viral DNA measurement (in Australia until recently only specialists could order this expensive test).

There are five commonly used serological tests for HBV. The surface antigen (HBsAg) indicates current Hepatitis B infection. It says "you have hep B now". It is found in serum during the incubation period before symptoms, and persists unless antibodies develop to the surface antigen (anti-HBs). Persistence of HBsAg defines chronic HBV and presence of anti-HBs indicates immunity to HBV infection (either by clearance of surface antigen, or by vaccination). Anti-HBs says "you don't have hep B and you can't get it anymore". * Sometimes anti-HBs wanes to undetectable levels in a person who has immunity to HBV, but there is still immune memory and anti-HBs rises to any immune challenge.

(* but see exceptions below)

The HBV core antibody (anti-HBc) develops early after HBV exposure and generally persists for ever: it just indicates previous exposure, and doesn't imply immunity (in this way it resembles HCV antibody). It says "HBV was here - and may still be here".

There are also tests for the HBV "e" antigen and its antibody (HBeAg and anti-HBe). HBeAg is a marker of viral replication and infectivity, and means there are high levels of HBV DNA in the blood. The person with HBeAg is either in the "immune tolerant" or the "immunoactive" phase of HBV. Loss of the HBeAg with appearance of anti-HBe generally indicates that the HBV DNA levels have been suppressed, the so-called "immune control phase" of hepatitis B - in this case the liver function tests will usually be normal.

However absence of HBeAg and presence of anti-HBe also occurs when a person moves into the "immune escape phase", where HBV-DNA levels and the ALT rise again.

Putting these tests together, HBsAg with HBeAg means chronic HBV with high infectivity. HBsAg with anti-HBe generally means low infectivity, undetectable DNA and "immune control" but can point to "immune escape phase", with high HBV-DNA levels and liver inflammation.

HBV is an oncogenic virus, and unlike HCV, can cause hepatocellular carcinoma (HCC) in the absence of cirrhosis. Of all people with chronic HBV, about 30% will go on to cirrhosis, and 5-10% will go on to HCC. Of people with HBV cirrhosis, about 1 in 4 will go on to liver failure within 5 years.

Primary prevention for HBV depends on screening and vaccination of high risk individuals and universal vaccination of infants. People who may have poor immune response (HIV/haemodialysis patients) or who may be at higher risk (people with existing liver disease, health care workers) should have anti-HBs checked after the usual 3-vaccine course, and may need a booster. People, including infants, who have accelerated HBV vaccination schedules should also have a booster at 12 months. Immunocompetent people generally do not need boosters even if anti-HBs wanes. However, 5-10% of people fail to respond to vaccination, and these people should be advised that they may need passive vaccination with HBV immunoglobulin (HBIG) within 72 hours if they are exposed to HBV.

HBIG should be given to babies of HBsAg mothers within 12 hrs of delivery, and standard vaccination carried out.

The second part of this summmary will present treatment issues and case studies:

Dr Matthews pointed out that HBV is a fluctuating disease, and that for the majority, chronic HBV is never "cured". One might wish for HBsAg seroconversion as a goal of treatment, but this currently impracticable. For this reason it is best to think of and manage HBV as a chronic viral illness like HIV, rather than merely a viral hepatitis.

(Note: the majority of adults after acute infection, and a small percentage of people each year after chronic infection, may spontaneously clear HBV by developing anti-HBs. Usually this amounts to spontaneous "cure", however even then HBV can return in situations of immunocompromise eg HIV infection, chemotherapy).

Overall, about 60% of people with HBV can be managed by regular monitoring and attention to risk factors for disease progression, while 40% need antiviral treatment. However, people can move from one group to the other.

The goals of therapy can be defined in several ways, but the essential aim is virological suppression to allow histological improvement, and prevention of HCC and end stage liver disease.

For HBeAg positive individuals, a desirable end-point is anti-HBe seroconversion, with loss of HBeAg. For HBeAg negative individuals, suppression of viral DNA is the essential aim. For all individuals, normalisation of ALT is a good indicator of reduced hepatic injury.

Current therapeutic agents are divided into two types, immune modulators (alpha interferon) and antiviral agents (nucleoside analogues NAs). The development of pegylated interferons and a wider range of NAs has improved therapeutic options and outcomes.

The two main therapeutic questions are: whether to use an immune modulator vs an antiviral; and whether to use one or two agents (immune modulator plus NA, or two NAs).

The benefits of interferon alpha monotherapy for HBeAg positive patients are clear, with reduced rates of cirrhosis and HCC, and increased survival. The treatment aim is to "push" these people into the "immune tolerant" phase of HBV. The advantages of interferon are the finite duration of treatment, durable treatment response (when it occurs), the high rate of HBeAg loss (around 30%), and loss of HBsAg in 3%-8%. Drug resistance does not develop. Disadvantages include unpleasant side effects, high cost, and lower responses with some genotypes and where there is high-level viraemia.

Nucleoside analogues for HBV include lamivudine, adefovir, entecavir, telbivudine, tenofovir and emtricitabine (the first 4 are currently licensed for HBV). The archetypal NA, lamivudine, effectively suppresses viral replication, with reduced liver inflammation and improved liver histology. In up to 50% of HBeAg positive people, it also produces seroconversion to anti-HBe ("pushing" into the immune control phase) however this may take as long as 5 years. For people who do not achieve eAg seroconversion (ie do not develop anti-HBe) the therapy must be continued indefinitely, as it must also for people who are eAg negative (in the "immune escape" phase).

Unfortunately, viral resistance to lamivudine develops almost universally with time, especially where there is HIV coinfection. In this situation, alternatives are adefovir, and entecavir; the latter is a more potent suppressor of viral replication, and resistance appears to be less of a problem. It may increasingly be first line therapy for many people.

Nucleosides analogues have the advantages of oral delivery with minimal side effects. Treatment is less expensive than interferon, but not when given long-term. There is potential for multidrug resistant organisms, especially when NAs are used sequentially.

Management of chronic HBV depends on a thorough assessment including liver function, serological markers, HBV DNA, sometimes liver biopsy (or fibroscan), and cofactors for disease progression (HCV/HDV/HIV). People should be vaccinated for HAV, given clear advice on transmission, and problems of alcohol, tobacco, obesity and diabetes dealt with if possible.

Specific treatment is recommended for:• HBeAg positive people who have elevated ALT, and HBV DNA > 20,000 IU/ml• HBeAg negative people who have abnormal ALT, HBV DNA > 2,000 IU/ml, and necroinflammation/fibrosis on biopsy• Cirrhotic patients with any level of measurable HBV DNA

Initial Treatment Strategies

Immune modulators may be preferred for healthy people < 60 years, with no cirrhosis, a baseline HBV-DNA > 1010 copies/mL, and ALT > 2-3 times normal, and who have genotype A or B (the more responsive genotypes)

Nucleoside analogs can be used for any age adult, for any genotype, with or without comorbidity (including cirrhosis with or without decompensation), a baseline HBV-DNA 109 copies/mL and ALT > 5 times normal.

In people with advanced HBV it is important to manage the viral infection aggressively and refer early for transplant assessment. Any patient with cirrhosis should have 6-monthly screening for HCC, using alphafetoprotein (AFP) and abdominal ultrasound (in cases of doubt triple phase CT/MRI). The following groups should also be targeted for HCC screening, regardless of their stage of liver disease: Asian men over 40 years of age; Asian women over 50 years of age; Africans over 20 years of age; and people with a family history of HCC.

Case studies (with apologies to Hanna Barbera)

Barnie is 36. He has a 12 year history of heroin injecting, previous buprenorphine maintenance on several occasions usually of short duration and with subsequent relapse His current BMT episode is 5 months, dose 8mg/day and he keeps using heroin.

He says "I've had hep B and hep C for years." He sometimes shares fits because 'What's the point? I've got both already." He drinks alcohol most days, 30-120g.

He is HCV seropositive and HCV-RNApcr positive; HIV negative and HBsAg positive. His ALT is 72, AST 60, GGT and other liver function tests are normal. After strong advice, he ceases sharing injecting paraphernalia, but he continues drinking most days.

On subsequent testing his ALT remains elevated. His second HCV-RNA pcr test is negative. He remains HBsAg positive, HBeAg positive and Anti-HBe negative. How should he be managed?

Comments: if his HCV-RNA remains negative, he may have ceased reinfecting himself with HCV and cleared the virus. He has "immunoactive" HBV with alcohol as a risk factor. Progressive liver fibrosis can occur in the "immunoactive" phase, and alcohol and periods of HCV infection may have contributed to this. Liver biopsy staging may be helpful here. If he does not have cirrhosis already, could have interferon treatment to try to push him into the "immune control" phase of HBV. He should be strongly encouraged and supported to stop alcohol entirely, and this would be a condition for interferon treatment. An alternative would be long term NA treatment.

Fred is 37 and has been on MMT for 6 years. He has not injected drugs for 5 years, and has practically given up alcohol, which he used to drink regularly 30-80g/day. He smokes 40 roll-your-own cigarettes a day.

He is HCV and HIV seronegative but has HBsAg, with both e antibody and antigen. He thinks he got HBV from injecting, but doesn't know when. His ALT and AST are usually normal or mildly elevated (<80) and other liver tests are normal.

During ketoconazole treatment for toenail tinea his transaminases rose to over 500, with other LFTs normal. He stopped the ketoconazole but his transaminases remained elevated (about twice normal) over the next 2 years. He remained positive for HBsAg, and anti-HBe, and became negative for HBeAg.

Fred is against "western" treatment for his liver, and gets herbal treatments from a homeopath in Victoria who runs a telephone consultancy. The cost of these medications ranges up to $60/month plus $60 for each phone consultation. Fred pays the phone bill.

Comments: when he had both Anti-HBe and HBeAg, he was apparently seroconverting for e antigen, thus follow up showed loss of HBeAg. As his transaminases remained elevated, HBV-RNA testing was subsequently done, showing <2,000 IU and confirming "immune escape" phase. He therefore needs long term nucleoside analog treatment. There is no evidence for the benefit of homeopathic treatment, and this should not distract him from the antiviral treatment which he needs to prevent severe liver damage. His smoking is a risk factor for HBV disease progression.

Pebbles is a 32 year old transsexual who is on BMT for heroin addiction. She has always smoked her heroin and never injected drugs. She was born in Asia: her blood tests show anti-HBc and HBsAg but her liver tests are always normal. She says all her family back home have Hep B. She has anti-HBe and does not have the HBeAg. She asks "I am going to get liver cancer?"

Comments: she was probably infected early in life, and is now in the "immune control" phase of HBV. She is at risk of hepatoma even if she remains in the "immune control" phase, and should be screened every six months after the age of 40, or from now if there is a family history of liver cancer. Although it is unlikely she has cirrhosis on this evidence, it is possible. If liver biopsy or fibroscan showed evidence of cirrhosis she should have hepatoma surveillance.

Dino is 38 and is on MMT. He has cleared HCV, is HIV negative and had a full course of HBV vaccination 6 years ago. After a recent test showing negative for anti-HBc, anti-HBs and HBsAg, he had two more HBV shots, but remained anti-HBs negative 6 months later. He asks “What's the point of me having all these tests & these expensive shots if they don't work?"

Comments: 5-10% of people fail to respond to vaccination, and these people should be advised that they may need passive vaccination with HBIG within 72 hours if they are exposed to HBV. HAV vaccination should be offered if he is not immune.

Betty is a 54 year old injecting drug user on MMT with regular alcohol use (40-60g/day most days). She is HCV and HIV seronegative. Her HBV serology is: anti-HBc positive, anti-HBs negative, HBsAg negative, eAg and anti-HBe also negative. Her ALT and AST are always high, with ALT>AST. Should she have HBV-DNA testing?

Comments: with isolated core antibody, it is most likely she has waned surface antibody, and a challenge with a vaccine may demonstrate this with anti-HBs becoming measurable. It is also possible she has chronic HBV and low level HBV-DNA despite not having measurable surface antigen. However, it is unlikely that such low levels of DNA would cause clinically significant disease. HBV-DNA testing is probably not needed but she should be advised to reduce her alcohol to safe levels and liver tests followed up 6-monthly.

22 July 2008

Dr Julian Trollor is Senior Staff Specialist Neuropsychiatrist at the Neuropsychiatric Institute, Prince of Wales Hospital and Senior Research Fellow of the Brain Ageing Program at the University of New South Wales. He established a clinic for the assessment of adults with possible ADHD in 1995. This clinic now operates as a tertiary service, providing second opinions in difficult cases.

Dr Trollor began his presentation by recounting his own experience of filling out a pop-up box which once appeared unbidden on his computer screen. Dr Trollor (who does not have ADHD) was informed...."the responses you have provided indicate that your symptoms may be consistent with Adult ADD. It may be beneficial for you to talk with your healthcare professional about an evaluation.” The pop-up was sponsored by a manufacturer of a pharmaceutical for ADHD.

Dr Trollor pointed to the growing popular awareness of Adult ADHD (A-ADHD), with ‘self diagnosis’ being common, shared controversy with its childhood counterpart, and community fears about treatment with a potential "drug of abuse".

ADHD is a "neurodevelopmental disorder of childhood onset characterised by impairments in cognitive function (inattentiveness), excessive motor behaviour (hyperactivity) and impaired behavioural regulation (impulsivity).” It is common, with high co-morbidity, and it is often overlooked, despite being relatively easily treated, with treatment improving outcomes.

Evidence for the validity of the entity A-ADHD has increased greatly in the last decade and is found in cross sectional, longitudinal and epidemiological studies, family & genetic studies, and neuro-psychological, -physiological, -endocrine and -anatomical studies.

Despite progress in understanding of A-ADHD, clinical diagnosis remains problematic: there is no single criterion marker; the core symptoms are dimensional (or spectrum) rather than categorical; co-morbidity can confound diagnosis; the requirement for retrospective childhood diagnosis may create difficulties; the key descriptors are ubiquitous; and the requirement for “significant impairment” is arbitrary. Diagnostic tests are often used but they lack specificity.

The DSM IV CRITERIA are listed in the appendix (see Redfern Clinic website). Briefly, the person must have (for the primarily inattentive type) six or more inattention symptoms as well as (for the combined type) six or more hyperactivity/impulsivity items for at least 6 months to a degree that is maladaptive. Some symptoms must be present before 7 years of age, impairment must be present in at least two settings, and symptoms do not occur exclusively during the course of a pervasive developmental disorder, psychotic disorder and (as always in DSM-IV) are not better accounted for by another mental disorder.

Symptoms can be grouped in four types:

1. attentional, with difficulty sustaining attention (during lectures, reading, in conversation, at work), easily distractability (eg by extraneous sounds, activity), day-dreaming, making careless mistakes - the primarily inattentional type is more common among women.2. organisational, often losing things, forgetting day to day activities or appointments, having difficulty organising tasks, following verbal instructions - these may be more pronounced in unstructured settings, and therefore may become more problematic in adults, upon leaving a structured setting like school/college.3. hyperactivity, being always “on the go” physically, being fidgety or restless, having difficulty relaxing, having racing thoughts or many ideas, taking on multiple tasks at once without finishing many.4. impulsivity, talking excessively, making tactless comments, interrupting conversations, difficulty waiting turn, taking risks (eg driving, thrill seeking, financial risks), explosive temper, irritated easily by minor frustrations, quick mood changes.

Hyperactivity may be less marked in adults in whom the hyperactivity may be more a phenomenon of mental cluttering, akin to a sense of continuous "noise" - quite distinct from anxiety. A meta-analysis of follow-up studies of children with ADHD showed an age-dependent decline in ADHD symptoms: 65% experienced partial remission in adulthood, with full ADHD diagnosis persisting in approximately 15%. The severity of ADHD symptoms in childhood appears to predict persistence into adulthood.

A large cross-national survey estimated adult ADHD prevalence across ten countries to be 3.4% (range 1.2-7.3%); one US study estimated current prevalence of adult ADHD at 4.4%. As Dr Trollor pointed out, these estimates suggest that A-ADHD is one of the more common mental disorders.

ADHD is a condition with a high genetic loading - family studies suggest 80% of ADHD symptoms can be attributed to genetic factors - with genetic-environmental interactions also playing a role, especially disrupted attachment, early abuse, and chaotic environment. The candidate genes are those involved in motor activity and attentional processes, and include DAT gene (SLC6A3), COMT (Catechol-O-methyltransferase), DBH (Dopamine beta-hydroxylase) and dopamine receptors (especially DRD4), however no single gene accounts for more than 5% of the phenotypic variance of ADHD.

Adult ADHD has major consequences: adults with ADHD are less likely to be employed full-time and more likely to have unstable work records, have significantly lower household income, have fewer close friends, more difficulty sustaining relationships and higher likelihood of having contracted a sexually transmitted disease. They are more accident prone (more traffic violations, severe accidents, more likely to be ‘at fault’), and have higher medical costs.

Diagnosis

In making a diagnosis, it is important to consider the motive/catalyst for presentation, whether owing to legal & forensic issues, a transition from a more to a less structured environment, or on cessation of substance use. Some adults come forward for assessment following diagnosis of their children. Self diagnosis is not a reliable indicator of the presence or absence of ADHD

The diagnostic pathway is to assess current symptom profile, severity and impact, to establish and corroborate childhood diagnosis (from self-report, parental and school reports, previous psychological or medical assessments) and to evaluate co-morbid (or diagnostically confounding) conditions - people with ADHD have increased risk of a diagnosis of antisocial personality disorder, of anxiety disorders, major depression and substance use disorders.

Bearing in mind the partial remission of ADHD in many or even most adults, it is important to consider the actual impact of symptoms on the patient's social, occupational, educational or family life as well as their current coping strategies. Many people cope well with or are untroubled by having features of ADHD and it is not uncommon for people with ADHD to be less likely to complain than their partners or family.

Establishing a retrospective childhood diagnosis is often a challenge, especially for people with major psychosocial problems including substance use disorder (SUD) who may have chaotic histories and be estranged from family. Where possible, informant interview can provide corroboration of the nature and extent of both current and past symptoms. Evidence can be gleaned from academic records, number and type of jobs, history of impulsive infringements, self esteem and interpersonal problems (resulting from impulsivity, poor anger control and organisational skills), and patterns of drug use which may suggest self-medication of symptoms. Sometimes there is a suggestive ‘paradoxical response’ to street amphetamine - ie a calming effect rather than stimulation.

Further assessment may include the use of rating scales, and require physical examination, bloods testing including thyroid function, urine toxicology, EEG, CT/MRI of the brain (a history of head injury may be common in people ADHD owing to their accident proneness, but brain injury may also sometimes mimic ADHD symptoms), and neuropsychological examination including CPT. Not all of these will be required in every case.

Substance Use Disorders and A-ADHD

The epidemiological relationship between substance use disorders (SUD) and A-ADHD is bi-directional, with increased rates of SUD in ADHD clinic samples (for alcohol 17-45%, other drugs 9-30%) and of ADHD in SUD clinic samples (around 25%).

Relative risk of SUD in follow-up of ADHD cohorts is increased up to five-fold, with earlier and increased use of alcohol, tobacco and other substances in adolescents with ADHD compared to controls, and ADHD in childhood and adolescence a significant predictor for later substance use - the risk is greater if the individual has conduct disorder or mood disorder. The relationship of with childhood ADHD is strongest for tobacco smoking, and it is likely a sub-group of individuals with ADHD self-medicate with tobacco: nicotine has been successfully trialled as an intervention.

People who have both SUD and ADHD have poorer outcomes. However, people treated with stimulants in childhood and/or adolescence have an equivalent or lower incidence of SUD compared to those untreated, and the use of stimulant medication to treat people with ADHD does not increase the risk of developing substance use disorder.

It is preferable to perform diagnostic assessment during long-term abstinence (whereby opioid substitution treatment with abstinence from other problematic substance use can be considered abstinence) and, as with other co-morbidities, active SUD should be addressed prior to specific ADHD treatment. It should be borne in mind that ADHD medications have no demonstrated efficacy for the treatment of ADHD where there is co-morbid SUD, nor have studies been conducted of use of psychosocial interventions.

Dr Trollor recommended (and feedback is welcome about) the Draft Guidelines for the Assessment and Management of Attention Deficit Hyperactivity Disorder (National Health and Medical Research Council and the Royal Australasian College of Physicians) accessible at http://www.racp.edu.au/ ( follow link under ‘announcements’).

From these guidelines, the following are some key recommendations for best practice for assessment and diagnosis of ADHD in adults when co-morbid SUD is present:

People with personality disorder and/or substance abuse should be referred for evaluation of ADHD if they present with a significant level of hyperactivity / impulsivity accompanied by inattention.Medication treatment for ADHD co-morbid with substance misuse should only be provided by a medical practitioner with expertise in both conditions.ATX should be the first medication trialled if there is co-morbid substance abuse.

Management of A-ADHD

Dr Trollor's approach to management is to create a hierarchy for interventions, generally treating pressing co-morbid conditions first, as these may increase the expression of ADHD symptoms, and providing for further observation in cases where the diagnosis is uncertain.

Against a backdrop of a rapid rise in prescription rates, unease about use of stimulants arises from several considerations. With continuation of treatment from childhood there are potentially decades of exposure to stimulants. Should this be open-ended? What are the risks of psychological dependence, and harmful use/dependence given the high psychosocial and substance comorbidity in adults with ADHD?

Stimulants are effective in adults with ADHD although the number of studies is small. Available efficacy data for adults give response rates between 25 and 78 percent for methylphenidate (MPH), in a similar dose range as for children, and a modest literature suggest similar efficacy for dexamphetamine (DEX) - there is no direct evidence to support use of high or very high doses of MPH or DEX.

Current evidence suggests the use of stimulant medication to treat people, including children, with ADHD does not increase the risk of developing substance use disorder. However, there is evidence of diversion and misuse of prescription medications for ADHD among school students and college students, with between 16 and 29 percent of students on stimulant medication having been asked to give, sell or trade their medication at some time. While some individuals report using diverted stimulants to self-medicate for ADHD symptoms, others use them to enhance performance, or for their euphorogenic effects.

Dr Trollor advises stimulant treatment should be reserved for people with pervasive symptoms causing significant difficulty, and where clear goals can be identified, the patient is motivated to work on broad range of solutions and where adequate follow-up and monitoring is available.

Stimulant treatment is relatively contraindicated where ADHD symptoms are present but are not the primary problem, where the clinical diagnosis conflicts with patient ‘self-diagnosis’, where there is severe co-morbid psychosis or mood disorder, or continuing problematic substance use. One warning signal is where the patient has many past prescribers of stimulants.

Non-stimulants, long-acting stimulants or anti-depressants are preferred to short acting stimulants, which are strongly reinforcing drugs. Pharmacotherapy should be trialled for effectiveness on an individual basis and carefully monitored for benefits and adverse effects; a contract for stimulant treatment may include regular review (possibly including urine toxicology - a moot point at this seminar) and an ongoing goal of abstinence.

Atomoxetine is a predominantly presynaptic noradrenaline transporter inhibitor without euphorigenic and reinforcing properties, with several studies showing benefit in children and adults. There is also a small number of studies for buproprion (an indirect NA & DA agonist), likewise with a low “abuse potential”.

Stimulant Dose

There are no trials of ‘high’ or ‘very high’ stimulant doses in adults with ADHD, and low dosing appears to be appropriate for most individuals. Dr Trollor recommends cautious titration eg commencing at DEX 0.15mg/kg/day or MPH 0.3mg/kg/day and aiming for DEX < 0.5mg/kg/day or MPH <1.0mg/kg/day. For the stimulant-naive patient, Dr Trollor recommends commencing DEX 5mg mane & midi (or MPH 10mg mane & midi). Smaller doses may also be required if patient on other psychotropics or has comorbid anxiety or sleep disorder. Animal models demonstrate a biphasic response to DEX: low doses (DEX < 1.0mg/kg) reduce, and higher doses DEX 1.0-5.0mg/kg increase, locomotor activity, which may correspond to a “high” in humans. As stimulants lower the seizure threshold in animals, are associated with (transient) emergent ‘tics’ in 10% of stimulant treated children, elevate pulse and blood pressure (low dose stimulants increase BP by an average of 3-5mmHg) low doses and close monitoring are indicated where there is co-morbid tic disorder, hypertension or seizure disorder. Although psycho-stimulants can induce paranoid delusions, auditory & visual hallucinations, this is mainly seen with intravenous use. Inter-individual pharmacokinetic variability (especially for MPH, where peak serum levels vary up to five-fold) provides an argument for a trial of higher doses in some individuals with non response to low doses - monitoring stimulant levels may be helpful, as may a second opinion. One difficulty is how to monitor response, whether subjectively or using self rating scales, observer rating scales, or neuropsychological/neurophysiological testing. Many people will feel better using low dose stimulants, regardless of whether they have ADHD or not.

This conundrum was illustrated in a complex case study presented in the second half (see separate posting). Some parting questions: how can such a prevalent condition, especially in children, be conceived of as a disorder? In an evolutionary sense, does ADHD confer an individual or collective biological advantage? In an anthropological sense, does it represent a failure of adaptation to modern life? Summary by Richard Hallinan, based on Dr Trollor's presentation and powerpoint file.

Dr Jurd commenced by almost stating the obvious: the problem of addiction starts with the brain. The origin of the behaviour does not lie in reasoned thoughts, which are late in evolution, but in reward pathways, organised in the hind-brain. From this ancient part of the nervous system, the responses are transferred to the frontal lobes where conscious thoughts, decisions and deductions are made regarding diverse ways to satisfy the more primitive urges. While most reward pathways are related to survival and procreation, drug use mimics such responses chemically, causing satisfaction, pleasure and desire to repeat the experience. The concept of craving was discussed in depth - it is not easy to define and perhaps best to simply call it ‘the motivation to use the drug’.

Equally, a definition of clinical or behavioural ‘salience’ is difficult, yet it is crucial to understanding and defining addiction, first clearly done by the redoubtable Griffith Edwards. Dr Jurd suggested one way to define ‘salience’ is to look at the person’s ‘top-40’ items of interest which for non-addicted people would range across a variety of things from food to music to work, family and hobbies. For the compulsive drug user or alcoholic, gambler, etc this would be a very short list, largely related to their drug or behaviour of interest. This is the ‘narrowed repertoire’ of drug use behaviour.

We were told of a recent pivotal study by Anne Rose Childress working at Philadelphia with Charles O’Brien’s group. They found significant brain responses on real-time PET scanning from ‘split-second’ projections of drug-related images, despite them not being seen or recognised consciously in a group of 22 long term cocaine users. These were also closely correlated with drug, violence or sexually explicit images shown several days later in relevant cases (and not in controls). So, despite not realizing it at the time, these long-term cocaine users’ brains had registered the brief images unconsciously and committed them to memory. Thus for the first time we have evidence of addiction related cues and/or priming occurring ‘outside awareness’. There was also some corroboration of this remarkable finding from another study involving similar brain responses to cues for ‘‘unseen’’ monetary rewards (Pessiglione). The advertising industry may have known of these matters for years!

Decisions in adolescence are agreed to be most important in learning and memory, and some regard drug addiction as an ‘illness of youth’ [cf Stanton Peele ref below]. We were told that there are maximal numbers of synapses in the adolescent brain which then decrease with age. Synaptic structures are highly dynamic, and adult brains are able to make new cells. Both exercise and stroke can lead to increased neural production and brain cells move towards the injury site. All of this is contrary to traditional teaching about the CNS being unable to repair or replace damaged areas.

Addiction is not simply withdrawal, but craving, the inclination to use, the very nature of dependence and a whole clinical syndrome which persists, sometimes well after drug/alcohol use has ceased. DSM defines ‘early remission’ as up to 12 months. We were told that addiction is common, has social and medical impacts, as well as numerous psychiatric complications.

There must be a system of reward, hard-wired into the mammalian brain where intuitively certain people and/or events are memorable, striking and causing a ‘yearning’. And such a system would just be normal. Dopamine has been identified as the relevant neurotransmitter.

However one defines them, ‘cravings’ lead to the conscious motivation to seek and use the drug, with a euphoric recall, and with often pleasant associations. “This feels sooo … good”. This is the case for both stimulatory and sedating drugs. Dopamine from the nucleus accumbens is crucial for reinforcement and reward; attention, memory and learning. These mesolimbic pathways are not unique to opiates but are similar for nicotine, alcohol, benzodiazepines, stimulants, etc.

The next result is to trigger ‘yearning’ for the experience to be repeated. Drugs excite the reward pathway and this then leads to addiction. At a certain point the individual becomes aware of the dangers and the illogical nature of their behaviour, yet continues with it. Similarly, they may be able to rationalise with a counsellor, doctor or family member that it is harmful to continue (cortical), yet the behaviour persists (driven by limbic pathways).

We were shown a familiar brain diagram from The New England Journal of Medicine: Neural Reward Circuits Important in the Reinforcing Effects of Drugs of Abuse [Cami J, Farre M. 2003 349:975-986].

Stimulants may also cause direct stimulation of dopamine production. On the other hand, sedatives inhibit the production of inhibitors of dopamine and so lead to increased dopamine concentrations. Thus in the reward pathway all drugs lead to increased dopamine at critical points in the hind-brain and so lead to increased learning, attention and focus on the drug use.

Aversive Agents

Disulfiram does not affect the dopamine pathway, but has its action through the frontal lobe using logic and reasoning. With this the person learns that “it is dumb to take alcohol with this”, and so even when cravings are strong the addict may choose not to consume alcohol, knowing the likely consequences.

Agonists/Replacements

Most of these provide a longer acting form of the drug which avoids the cycle of intoxication and withdrawal. For example methadone is a long half life drug, decreasing heroin use and improving quality of life. The person learns that they simply do not need to use additional opiates as there is little gain.

Nicotine is the same drug, with a safer delivery of drug via patches, gums and inhalers. Post-myocardial infarct patients do better on patches.

Dexamphetamine - there is no pharmacological basis to change to this from methamphetamine as the half-life of ‘dex’ is 10-12 hours compared to 9-15 hours for methamphetamine. A longer acting form may be more appropriate for addiction treatment.

Benzodiazepines – theoretically for alcohol but they are not satisfactory, both are disinhibitory agents, acting on GABA receptors.

Naltrexone – a long acting opioid antagonist, works when taken but does not chemically modulate cravings for opioids (might do so psychologically according to Brewer). For alcohol with time it can modulate cravings but unlike disulfiram the person will not become ill if alcohol is consumed.

Rimonaband – cannabinoid antagonist - not yet available in Australia – used overseas for obesity(?).

These take time to work, and act less on receptors but modulate other areas which then lead to change in receptors and/or their neurotransmitters.

Acamprosate modulates the balance of GABA. We were reminded that this drug is really only of benefit for those wishing to cease alcohol use completely whereas those on naltrexone are more likely to be able to manage controlled drinking better (although this is not approved under PBS prescribing criteria). In a similar way in depressives, SSRI drugs also take time to have their clinical effects, rather than a chemical effect on receptors which theoretically occurs straight away.

We were then brought back to the traditional in-patient treatment of alcoholism and drug addiction, something which is now rare as authorities have closed down many detox and rehab wards. The justification has often been that they were “not cost-effective”. Dr Jurd quoted the highly reputed “Project Match” which found double the rate of abstinence at one year in those who received an in-patient stay as part of their treatment when compared with those who only received out-patient services. Note that entrants were not randomised so the significance is limited to an non-causal association.

Two case histories were then presented and ‘work-shopped’ in some detail:

Case 1: A youth with excess alcohol use causing serious health, legal, and social problems.

Case 2: A middle-aged set-in-his-ways professional with smoking and alcohol excess with hypertension. He stopped nicotine after 12 months but unable to decrease his alcohol.

Case 1: A youth with excess alcohol use causing health, legal, and social problems.

• Your 18 yo patient Mark faces serious charges related to two events of driving under the influence of alcohol since his 18th birthday - the second was high range BAL, the accident with near fatal consequences but only mild injury (a broken clavicle).• He has a number (3 or 4) of prior arrests for alcohol-related offenses (drunk and disorderly) during 2007, however these were handled by the police with warnings, no fines and no convictions recorded.• He was treated at St Vincents ED for severe lacerations to his chest and abdomen from diving while intoxicated into water at Darling Harbour earlier this year.• Blood tests from hospital after his recent car accident are consistent with alcoholic hepatitis (AST 74, ALT 40, GGT 104).• Mark gives a history of drinking alcohol regularly from age 15, and only occasionally before that. In his last year of school (Year 10, 2006) he drank nearly every weekend at parties, typically as much as 12 schooners of beer (180g or18 standard drinks).• Although at that stage his drinking was not daily, he would often have 2-3 schooners of beer/day on the verandah after school, and would hide the bottles as his parents did not approve. Alcohol was freely available in the family home.• He left school in year 10 and worked as a plumbers’ apprentice, but couldn’t cope and now does concreting• His social life has been based on alcohol since age 15, all his friends drink.• By age 17 he was drinking after work typically 2-5 schooners (30-75g), and going into town nearly every weekend, where he admits he would drink until he was "blind" - he would lose count of how much he drank, and found it increasingly difficult to get drunk.• In 2008, with daily drinking part of the work culture, he was regularly getting heavily drunk.• he used to play a lot of football, now he couldn't be bothered. Alcohol took priority - "I chose the grog over my girlfriends"• since early 2007, he admits to feelings of loss of control, that he would like to be able to stop, feeling bad about needing beer to socialise (eg needing to take beers from the fridge with him when going out with mates).• There is no history of injecting drug use, and he does not use cannabis or amphetamines.• From primary school he was noted to be inattentive and hyperactive in class, and it was suggested he be assessed for possible treatment for attention deficit hyperactivity disorder (ADHD). His parents decided against such treatment.• There is no history suggesting conduct disorder as a child and no evidence of antisocial behaviours as an adult, other than under the influence of alcohol.• There is a strong family history of problematic alcohol use including three grandparents, one maternal uncle and Mark's own father, who has however now apparently returned to controlled drinking.• Mark has been warned by solicitor that he has a high risk of a gaol sentence.• What treatment is appropriate?

Case 2: A set-in-his-ways 45 year old journalist with smoking and alcohol excess with hypertension. He stopped nicotine after 12 months but unable to decrease his alcohol.

• Your patient Robert is a 44 year old journalist who is worried alcohol and cigarettes are going to kill him.• first alcohol was “shandy' as kid occasionally, then regular age 18, never alone at that stage, daily from age 21, still not alone, still sociable.• Binging was frequent in his 20s, after he finished work at 2.30pm, he went across to the “journos” or to the pub and drank with till he dropped.• Later his style was pub drinking alone for 2 yrs,• He has been drinking alone at home for the last 8yrs.• He was arrested for DUI after a MVA age 25, also charged once with drunken resist arrest.• He has had no recent alcohol related work or legal problems. He never drinks and drives anymore.• He is still –and contentedly - single and now works evening shifts till midnight, buys a six pack of beer and drinks it all from 12mn to 3am to get to sleep.• If he bought a case of beer, he is sure he would lose control.• He sometimes goes to footie on a Sat, tends still to stop at 6 beers. If he eats first, tends to stop.• He almost never drinks anything other than beer nowadays• He is quite happy with life, not interested in getting a social life, and really only concerned with his health, and not having a heart attack or stroke• He holds down his job without difficulty• Robert tried zolpidem for sleep when he tried alcohol abstinence for a week last year, short action was the main problem. He doesn’t think he has ever had alcohol withdrawal, but he hasn’t actually had a day off alcohol in many years except with zolpidem.• Cannabis experimented only, nil current. Nil IDU• Cigs 30-35 BH special filter; smoking since 17; 35 pack-years. Stopped smoking for 12/12 seven years ago, added 12 kg in weight. He tried NRT and failed.• His father was a heavy drinker in his heyday, but less now; also HIS father. Mother is a non-drinker. Of 2 sisters, one is a “social drinker”, other is teetotaller.• Robert has no other illnesses or symptoms on “systems review”.• OE: BMI 30.5; BP 160/95, pulse 78 regular• obese, smooth hepatomegaly, normal testicles and no g'mastia, koilonych, couple spider naevi only.• Non-tender abdo and heart normal to palpation and auscultation.• Height 169 cm, spirometry. 2.8/4.0 = 70%. (Pred VC 4.4 L, SD 0.5)• Bloods tests are all satisfactory other than lowish testosterone (9.8 on a 3pm collection) and cholesterol borderline (was normal two years ago). LFTs normal• Roberts is worried about his drinking and smoking, asks what he should do.• He doesn’t think he could tackle cigarettes and alcohol at the same time• He insists he really doesn’t want to stop drinking altogether, and hopes for “controlled drinking”.• What are the priorities?• Are medications appropriate for Robert?• What should you write back to his GP?• Robert’s blood pressure was stabilised on telmisartan and he set himself a goal of 3 schooners of beer/day and 2 alcohol free days per week. He agreed to try nictoine patches, two /day if needed.• He canceled his follow up appointment.• A year later he has returned, now 4 weeks off cigarettes using varenicline and seeks advice about his drinking which has not changed. He is still adamant that he wants to cut back rather than stop.• He has major dental; work coming up in a fortnight.

Professor Batey began by asking his audience to consider why this subject was being covered and also why he had been asked to speak on it. He pointed out that despite doctors being of a certain age and seniority, mistakes and miscalculations could still occur. A prevention strategy was essential using established safeguards. However, when these failed, such errors need to be dealt with appropriately and openly. This applies to doctors, nurses and all allied health professionals.No amount of renown could avoid this issue. No connection with great physicians, great institutions or fine academic reputation could help when things go wrong. We were told that despite a love of the profession and hitherto keeping out of the way of lawyers, none of us should become complacent or over-confident that it would remain that way.

Connections with great physicians could help in one respect: by following their examples in what they taught about good medical practice.The art and practice of medicine.The value of spending time with patients.The need to be ‘vulnerable’ rather than ‘all-knowing’.The absolute necessity to know what you are doing while admitting any areas of uncertainty.The reality that you might appear to be rude while still acting consistently and fairly.Patients may accept mistakes if you demonstrate that your are sincere and competent.

We can all name some great physicians we have worked with but it would be hard to match Dr Batey’s list of mentors: Allan McGuiness, Charles Ruthven Blackburn, Sheila Sherlock, Mr Michael Stephens, Dr Dick Richards. Those who worked at Sydney’s Prince Alfred Hospital or Sydney University may know three of these.

Some behaviours which patients and colleagues may sometimes overlook include:Aloofness.Use of long phrases no one can understand.Gruffness to the point of rudeness.Late for rounds but never missing them.However, this is contingent on the clinician displaying consistent excellence and reliability in the longer term, leading to the earning of respect.

In the field of Addiction Medicine there is another credential needed: A capacity to set boundaries. At this we were shown a slide of the Great Wall of China!In order to demonstrate some ways NOT to practise we were shown some cases from 2007:

Mr TMPresents with female partnerBoth on methadone: 65mg and 50 mg respectively for >10 yrsReceiving 4 take away doses.Neither are employed at present but both had been working in local area 12 months ago.No children at home

SO far so good butThey want to switch to oral Physeptone (methadone tablets) so they can just pick up scripts for 2 weeks supply.They also admit to not sleeping well and to using benzodiazepines regularly.No other major issues.

Main issue is a desire for increased “freedom”Totally anti-buprenorphine as partner had tried to change and failed miserablyThey talk constantly and when one stops to draw breath the other starts upThey have no insight into the issuesIt is late in the day

You weaken and write their first script of physeptone tablets, enough for 5 days “to see how they go”.

No no no!This is dangerousIt is unwarrantedIt is indefensibleAt this point……Is there a way forward??

Taking:Oxycontin 10 mg qidOxycontin 20 mg tdsOxycontin 40 mg prnAsks for proladone suppository twice a day to add to his pain relief program

You give him proladone

You have no idea what his pain is due to or indeed if he has pain at all.He is dependent, he has a “dog’s breakfast” of a management plan.BUT HE LOVES YOU for being so ‘caring’ !!!

The state pharmaceutical authorities may not be sympathetic - although after removal of the 2 month rule on opioid prescription in New South Wales in 2006 this may be ‘legal‘ even though it may be ‘poor medicine’.

Ms GG, aged 38.

Admitted to local hospital semi-conscious with signs of pneumonia.Uncertain what is happening but assessment reveals:Pneumonia of right lower lobe.Obtunded with pin point pupils.Injection marks L ante cubital fossa.Poor nutrition.

Lives with husband and 3 children 10, 9 and 4.She does not work, he is a motor mechanic.No major past medical problems.

Both she and he are on methadone program.She is on 80 mg/d and he 90 mg/d.Both get 6 takeaway doses per week.No safe storage sites at homeNo urine drug screens performed in past year.Pharmacist concerned regarding stability.Why does she get 6 T/A’s….. “Well, my husband gets them”.She responds to Narcan injection subcutaneously.Admits to injecting her doses.

Assessed for HCV and HBV and has both.1 Child has evidence of exposure to HBV.Vaccination program not completed.Is this all OK?? Should there be a full review of their dependency treatment?Mr BJ had Crohn’s disease for 15 yrs.Several recurrences when Inflammatory Bowel Disease (IBD) treatment reduced.Surgery x 3, fistula complicating this.Intermittent analgesia when in hospital.Tried heroin from friend “for pain relief”.Now on methadone program 50mg/d.Presents wanting pain relief from IBD.He convinces you of his pain.He asks for morphine injections prn.You are convinced of his need for pain relief.You write script for morphine ampoules and arrange for him to come in for doses when needed.He is found dead with signs of O/D. Not a good situation.

Ms HT is a 78 year old widowDependent on benzodiazepines you commenced years ago for insomnia.You become convinced benzos are bad for people and discuss trying to withdraw them which she refuses.

Admitted to hospital for an acute surgical problemShe experiences a significant withdrawal as no-one took a medication history. She decides that she was not adequately informed about the risks and sets a litigation process in motion.Who should have done more?

The next topic was “WHAT AM I DRIVING AT” which reminded us that it is OUR RESPONSIBILITY to ensure that patients are safe to drive, operate machinery and look after children while taking medication. All patients should be warned that new medication and changes in doses of existing drugs, including alcohol, may affect ability to perform adequately.

Professor Batey’s final advice to us was:Spend time taking a good history and performing a full physical examination.Communicate appropriately with your patients.Document findings and management plans in the notes.Evaluate progress rationally and regularly.Do not become enmeshed with patient stories rather than reality.Set boundaries clearly and compassionately.Seek peer support.Adhere to good clinical practice guidelines.Seek second opinions in unusual circumstances where guidelines may not apply.

6 February 2008

Dear Colleagues,Dr Lintzeris began by describing his shock at the state of skin and veins in a large proportion of drug users in England when he started a sabbatical session at the National Addiction Centre and Maudsley Hospital in 2003. He showed some unflattering photographs of lower limb ‘war-wounds’ inflicted by hypodermic needles, infections, impure brown heroin and neglect. Most of these people had ‘worked through’ their upper limb then moving to the legs so that 20 to 50% of patients in maintenance treatments were using their groin veins for access.

The street heroin used was of the Afghan or ‘brown‘ variety, needing lemon juice or acetic acid to make it soluble. Even then it was still caustic to the veins. Dr Lintzeris noted that there were very high rates of crack cocaine use in English patients, up to 40% smoking it regularly whilst in treatment. He quoted the mental and physical toll this took on the lives of addicts and their families. Alcohol and sedative use was also common. Notably, one common drug of abuse was amitriptyline (‘Tryptanol’, ‘Endep’), an antidepressant not known for recreational use in Australia.

Balancing the intravenous damage to some extent (and perhaps because of it) there was a high proportion of drug users who did not inject at all. Up to 40% were smoking, snorting or swallowing their drug of choice at the time of entering treatment. In Australia about 90% of addicts entering treatment are injectors.

Dr Linzeris noted two main differences in maintenance therapies. Dose levels were generally in the low range (30-50mg daily) and the medication was usually given as “take away” bottles of weak solution rather than being taken under supervision. The use of 1mg per 1ml solution had parallels with the common practice in Victoria of ‘topping up’ take-away bottles with up to 100ml of water or cordial to discourage injecting.

Some graphs were shown of methadone treatment in Victoria from 1985 when there were only about 100 patients in treatment. By 1996 there were nearly 4000, and by 2003 about 8000 patients on maintenance treatments. An early experience of 10 deaths in patients starting methadone has shaped the Victorian approach to treatment ever since (see Drummer 1990). Mean dose levels in Victoria have always been in the low range, around 40mg, and only reaching 50mg daily in recent years (NSW is around 70mg). We were told that there were essentially no public clinics in Melbourne and nearly all patients were treated in pharmacies from GP prescribers. This means no capacity for subsidised methadone treatment since all patients must pay for pharmacy dispensing which is normally from 3-5 dollars daily. Very few take-away doses were permitted (originally 3 single doses per month) although this is changing now under more flexible health department rules.

Next we were informed that 33% of 193 authorised prescribers had no active patients. Another 33% had from 1 to 10 patients only while just 15% of the busier prescribers were treating 69% of Victoria’s patients. Thus most of the dependency treatment service in Victoria relies on just 27 individual doctors! By contrast in 2005 NSW had over 500 prescribers and 16,000 patients with no one doctor prescribing for more than 150 patients. In England all doctors can prescribe methadone if they wish to.

Buprenorphine has had significantly greater uptake in Victoria than in the other states. After the first year of use (Jan 2002) there was just 10% of the total on buprenorphine according to some bar charts we were shown. By 2004 it rose to over 50% briefly and then dropped back slightly to 40:60 bup:meth since that time. One may speculate on the reasons, but they probably include the rigidity of the original methadone regulations in Victoria. There was widespread use of second daily buprenorphine even though this is not shown to be as effective as daily use.

In Victoria even the more complex patients with extensive needs and poor resources were still mostly managed by GPs and pharmacists as there are no comprehensive clinics with access to counsellors, psychology, vocational support, social work, etc. Dr Lintzeris called this the ‘minimalist’ model. On the other hand, he told us that considering the state of play in Great Britain, there was simply no model or ‘system’ at all! This was not quite fair since he then showed a pie chart demonstrating that one quarter of patients in GP prescribing (nearly all ‘NHS’), another quarter in ‘shared care’ between formal clinics and GPs with fully 50% of all patients now in formal ‘specialist programs’ (Community Drug Teams). While some of these latter can formally supervise doses, few pharmacies give witnessed doses.

Treatment access across the UK was highly variable and depended on GP willingness to prescribe. Waiting times for GPs is usually about 2 weeks but up to 3 months for Community Drug Team assessments. Proper, evidence based maintenance treatment (as per UK treatment guidelines) is the exception with most patients on low and reducing doses with sadly predictable results. A common practice is for 40mg daily to start with and reductions from there.

GPs in the UK also commonly prescribe codeine, dihydrocodeine and buprenorphine but more due to personal preference rather than patient need. This applies equally to injectable methadone which comprised 10% of all opioid treatment prescriptions 10 years ago but is less than that now, partly due to the 1999 “Orange” guidelines which were sent to every practising GP in the UK. Methadone tablets are also less used now with about 95% of maintenance medication being methadone in liquid form, mostly the watery and bulky 1mg/1ml solution. Injecting of methadone is rare, as in Victoria, presumably due to dilution of doses which is almost universal. Whether such measures have more benefits than drawbacks on balance has never been tested scientifically. Thus it would seem prudent to consider diluting (‘expanding’) doses in special cases but not ‘across the board’ until such evidence is presented.

Another disadvantage of non-supervised consumption in the UK is that the ‘black-market is flooded’. There is now a scheme whereby pharmacists are paid 1 to 2 pounds daily to administer doses of methadone; patients usually pay nothing. Over a third of patients attend once weekly (6 or 7 bottles dispensed) with a third attending daily (except Sunday) often taking a bottle home. Most of the reminder attend 2, 3 or 4 times weekly. There are no hard and fast rules to addiction treatment in the UK allowing much more professional freedom. Whether that is a good thing overall is a moot point considering the poor adherence to good prescribing practice over many years.

The scientific evidence shows that if take-away doses and less supervision were linked to demonstrated progress, such as urine test results, this was the most effective intervention as ‘contingency management’ by another name.

Dr Lintzeris mentioned the various risks of injecting methadone, overdoses, child deaths and the public perception of the drug treatment system generally. We were told that people could successfully inject the buprenorphine combination drug with naloxone, Suboxone (unpublished comparative study by Leslie Amass, CPDD 2000). Also Dr Lintzeris quoted reductions in the injecting of methadone in NSW and said that the reason behind this was not clear.

Crushing of buprenorphine tablets has been advised by some parties yet evidence is limited on the practice. It would seem logical in some patients who had been caught diverting tablets, yet it clearly will not solve all the problems of buprenorphine administration.

This returned us to some questions posed by Dr Hallinan before the seminar: Why do we have public clinics, private clinics and pharmacy dosing for supervised treatment in NSW? Along with prison programs, is this serendipitously world's best practice, or a ‘clumsy and vestigial hybrid’? Are we using a number of flexible treatment models for people in various circumstances, or limiting access to opioid maintenance treatments which could be given more effectively in another way? Later discussion and case studies dealt with issues surrounding "access block" in NSW.

Summary by Andrew Byrne based on Dr Lintzeris’ power point presentation, questions on the night and some comments from Dr Richard Hallinan.

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On this web site, Dr Byrne and colleagues have written summaries of many research articles, conferences and other events. These have been written largely to draw attention to peer-reviewed studies which may be relevant to clinical practice and public policy. While all care has been taken to be fair and accurate, readers are strongly advised to read the original publications before acting upon the information for clinical decisions.

Due to this brief form of communication, no responsibility can be taken for errors, mistakes or omissions.